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Immunomodulators: Dr. Kaushik Mukhopadhyay Assistant Professor, Dept. of Pharmacology Esi-Pgimsr
Immunomodulators: Dr. Kaushik Mukhopadhyay Assistant Professor, Dept. of Pharmacology Esi-Pgimsr
Immune
Immunosupression immunostimulation
Tolerance
MOA –
To effect longer-term responses, steroids bind to receptors inside cells; either these
receptors, glucocorticoid-induced proteins, or interacting proteins regulate the
transcription of numerous other genes
Curtail activation of NF-КB, which increases apoptosis of activated cells, key pro-
inflammatory cytokines such as IL-1 and IL-6 are downregulated.
Neutrophils and monocytes display poor chemotaxis and decreased lysosomal enzyme
release.
combined with other immunosuppressive agents to prevent and treat
transplant rejection.
graft-versus-host disease in bone-marrow transplantation.
Glucocorticoids are routinely used to treat auto-immune disorders such
as
RA
SLE, psoriasis
Asthma and other allergic disorders,
inflammatory bowel disease
acute exacerbations of MS (see "Multiple Sclerosis").
to block first-dose cytokine storm caused by treatment with
muromonab-CD3 and to a lesser extent ATG
Growth retardation in children,
Avascular necrosis of bone, osteopenia
Increased risk of infection
Poor wound healing
Cataracts
Hyperglycemia
Hypertension
PK-
• 20-50% bioavailability
• CYP3A4
USE –
• Clinical indications for cyclosporine are kidney, liver, heart,
and other organ transplantation
• Rheumatoid arthritis and psoriasis.
Nephrotoxicity,
GI complaints,
hypertension,
tremor,
hirsutism,
hyperlipidemia,
and gum hyperplasia
DDI - Sirolimus aggravates cyclosporine-induced renal dysfunction
Sirolimus is a macrocyclic lactone produced by Streptomyces
hygroscopicus
PK-
• Systemic availability is 15%
• A loading dose of three times the
maintenance dose will provide
nearly steady-state
• CYP3A4
USE –
• Prophylaxis of organ transplant
rejection usually in combination
• At risk of calcineurin inhibitor–
associated nephrotoxicity MOA
dose-dependent increase in serum cholesterol
Lymphocele, a known surgical complication associated with renal
transplantation
cyclosporine and sirolimus interact, and their administration
should be separated by time
Everolimus
chemically and clinically related to sirolimus but has distinct
pharmacokinetics.
The main difference is a shorter t1/2 and thus a shorter time to
achieve steady-state concentrations of the drug.
It is an imidazolyl derivative of 6-mercaptopurine
MOA –
cleaved to 6-mercaptopurine (via Glutathione),
A fraudulent nucleotide, 6-thio-IMP, is converted to 6-
thio-GMP and finally to 6-thio-GTP, which is
incorporated into DNA.
converted to additional metabolites that inhibit de
novo purine synthesis
Cell proliferation thereby is inhibited, impairing a
variety of lymphocyte functions.
PK –
Well absorbed orally
T1/2 = 10 mins (active metabolites)
USE-
adjunct for prevention of organ transplant rejection
Severe RA
ADR –
The major side effect of azathioprine is bone marrow suppression
increased susceptibility to infections (HSV),
hepatotoxicity, alopecia, GI toxicity, pancreatitis,
It is an ester of mycophenolic acid (MPA).
MOA –
MMF is a prodrug that is rapidly
hydrolyzed to the active drug, MPA
MPA - a selective, noncompetitive,
reversible inhibitor of inosine
monophosphate dehydrogenase (IMPDH),
IMPDH is an enzyme @ de novo pathway
of guanine nucleotide synthesis
B and T lymphocytes are highly
dependent on this pathway for cell
proliferation (others- salvage pathway)
PK –
The parent drug - within a few minutes. The t1/2 of MPA is 16 hours.
T1/2 = 10 mins (active metabolites)
USE-
MMF is indicated for prophylaxis of transplant rejection, and it
typically is used in combination (Glucocorticoid/Calcineurin)
off label - SLE
ADR –
Gut -
Hematologic – PRCA, leucopenia
Congenital anomaly
Methotrexate
Cyclophosphamide
Chlorumbucil
Origin Suffix =
Prefix Target
Subsystem mab
Inf Li Xi mab
Oma Li Zu mab Omalizumab
Ab ci xi mab Abciximab
Ri tu xi mab Rituximab